Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area

Cheng Xu,Shi-Ping Yang,Yuan Zhang,Ling-Long Tang,Guan-Qun Zhou,Xu Liu,Yan-Ping Mao,Rui Guo,Wen-Fei Li,Lei Chen,Ai-Hua Lin,Ying Sun,Jun Ma 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil after IC-1, all patients were categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropenia were associated with poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel– cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin ( 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin  1.33 were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Fusion Expression and Immunogenicity of EHEC EspA-Stx2A1 Protein: Implications for the Vaccine Development

Yan Cheng,Youjun Feng,Ping Luo,Jiang Gu,Shu Yu,Wei-jun Zhang,Yan-qing Liu,Qing-xu Wang,Quan-ming Zou,Xu-hu Mao 한국미생물학회 2009 The journal of microbiology Vol.47 No.4

Shiga toxin 2 (Stx2) is a major virulence factor for enterohemorrhagic Escherichia coli (EHEC), which is encoded by λ lysogenic phage integrated into EHEC chromosome. Stx2A1, A1 subunit of Stx2 toxin has gathered extensive concerns due to its potential of being developed into a vaccine candidate. However, the substantial progress is hampered in part for the lack of a suitable in vitro expression system. Here we report use of the prokaryotic system pET-28a::espA-Stx2A1/BL21 to carry out the fusion expression of Stx2A1 which is linked to E. coli secreted protein A (EspA) at its N-terminus. Under the IPTG induction, EspA- Stx2A1 fusion protein in the form of inclusion body was obtained successfully, whose expression level can reach about 40% of total bacterial protein at 25°C, much higher than that at 37°C. Western blot test suggested the refolded fusion protein is of excellent immuno-reactivity with both monoclonal antibodies, which are specific to EspA and Stx2A1, respectively. Anti-sera from Balb/c mice immunized with the EspA-Stx2A1 fusion protein were found to exhibit strong neutralization activity and protection capability in vitro and in vivo. These data have provided a novel feasible method to produce Stx2A1 in large scale in vitro, which is implicated for the development of multivalent subunit vaccines candidate against EHEC O157:H7 infections.

Molecular Cloning and Function Analysis of an Anthocyanidin Synthase Gene from Ginkgo biloba, and Its Expression in Abiotic Stress Responses

Feng Xu,Hua Cheng,Rong Cai,Lin Ling Li,Jie Chang,Jun Zhu,Feng Xia Zhang,Liu Ji Chen,Yan Wang,Shu Han Cheng,Shui Yuan Cheng 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.6

Anthocyanidin synthase (ANS, leucoanthocyanidin oxygenase), a 2-oxoglutarate iron-dependent oxygenase, catalyzed the penultimate step in the biosynthesis of the anthocyanin class of flavonoids, from the colorless leucoanthocyanidins to the colored anthocyanidins. The full-length cDNA and genomic DNA sequences of ANS gene (designated as GbANS) were isolated from Ginkgo biloba for the first time. The full-length cDNA of GbANS contained a 1062-bp open reading frame (ORF) encoding a 354-amino-acid protein. The genomic DNA analysis showed that GbANS gene had three exons and two introns. The deduced GbANS protein showed high identities to other plant ANSs. The conserved amino acids (H-X-D) ligating ferrous iron and residues (R-X-S) participating in 2-oxoglutarate binding were found in GbANS at the similar positions like other ANSs. Southern blot analysis indicated that GbANS belonged to a multi-gene family. The expression analysis by real-time PCR showed that GbANS expressed in a tissue-specific manner in G. biloba. GbANS was also found to be up-regulated by all of the six tested abiotic stresses, UV-B, abscisic acid, sucrose, salicylic acid, cold and ethylene, consistent with the promoter region analysis of GbANS. The recombinant protein was successfully expressed in E. coli strain with pET-28a vector. The in vitro enzyme activity assay by HPLC indicated that recombinant GbANS protein could catalyze the formation the cyanidin from leucocyanidin and conversion of dihydroquercetin to quercetin, suggesting GbANS is a bifunctional enzyme within the anthocyanidin and flavonol biosynthetic pathway.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings

Chen, Jia-Yan,Zhu, Hong-Cheng,Guo, Qing,Shu, Zheng,Bao, Xu-Hui,Sun, Feng,Qin, Qin,Yang, Xi,Zhang, Chi,Cheng, Hong-Yan,Sun, Xin-Chen Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Comparison of Serum Tumor Associated Material (TAM) with Conventional Biomarkers in Cancer Patients

Shu, Jian,Li, Cheng-Guang,Liu, Yang-Chen,Yan, Xiao-Chun,Xu, Xu,Huang, Xin-En,Cao, Jie,Li, Ying,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To compare expression level of serum tumor associated materials (TAM) with several conventional serum tumor biomarkers, eg., carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein(AFP), in selected solid tumors. Methods: Patients diagnosed histologically or cytologically with liver, breast, esophageal, gastric, colorectal or pancreatic cancers were enrolled into this study. After diagnosis, the level of TAM was determined by chemical colorimetry, and levels of conventional tumor markers was measured by chemiluminescence methods. Results: A total of 560 patients were enrolled into this study. No statistically significant difference was detected in TAM and the above mentioned tumor biomarkers in terms of their positivity and negativity ( P>0. 05). Conclusions: Detection of TAM in liver, breast, esophageal, gastric, colorectal, and pancreatic cancer patients demonstrates a good accordance with CEA, CA199, CA153, and AFP, thus suggesting that further study is warranted to verify whether TAM could be a surrogate for these conventional biomarkers.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

Yan Wan,Jing Wang,Jin-feng Xu,Fei Tang,Lu Chen,Yu-zhu Tan,Chao-long Rao,Hui Ao,Cheng Peng 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may causenumerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxiccompounds for the treatment of chemotherapy-induced side effects is necessary. Experimentsin vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic andeffective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity,cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on antioxidation,anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, suchas nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminalkinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signalregulatedkinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin(mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase(PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides onchemotherapy-induced side effects has not yet been published, we provide a comprehensive summarizationwith this aim and shed light on the future research of PG.

Attenuation of hyperoxic acute lung injury by Lycium barbarum polysaccharide via inhibiting NLRP3 inflammasome

Cheng-Ying Hong,Hua-Dong Zhang,Xue-Yan Liu,Yong Xu 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.10

Lycium barbarum polysaccharide (LBP), anactive component from Goji berry which is a traditionalChinese medicine, has anti-inflammatory and antioxidantfeatures. The aim of our study was to investigate whetherLBP has any role in hyperoxia-induced acute lung injury(ALI). Using a murine model of hyperoxia-induced ALI,we investigate the effect of LBP on pulmonary pathologicalchanges as well as Sirtuin 1 (SIRT1) and the nucleotidebinding domain and leucine-rich repeat pyrin domaincontaining 3 (NLRP3) inflammasome. Exposure to 100%oxygen for 72 h in male C57BL/6 mice resulted inincreased protein levels of tumor necrosis factor-a andinterleukin-1b in lung tissues, and aggravated lung histologicalalterations. These hyperoxia-induced changes andmortality were improved by LBP. LBP markedly suppressedthe activation of NLRP3 inflammasome bothin vivo and in vitro. Moreover, LBP upregulated SIRT1expression compared with vehicle-treated group. Importantly,knockdown of SIRT1 reversed the inhibitory effectof LBP on NLRP3 inflammasome activation in vitro. LBP meliorated hyperoxia-induced ALI in mice by SIRT1-dependentinhibition of NLRP3 inflammasome activation.

Generation of Selenoprotein with Glutathione Peroxidase Activity by Chemical Modification of the Single-chain Variable Fragment Expressed in a Single-protein Production System and Its Antioxidant Ability

Cheng Wang,Gang-Lin Yan,Shao-Wu Lü,Chun-Hong Sui,Yang Zhao,Ya-Wei Xu,Gang Zhao,Jun-jie Xu,Ping-Sheng Gong,Gui-Min Luo,Ying Mu 한국생물공학회 2013 Biotechnology and Bioprocess Engineering Vol.18 No.1

Glutathione peroxidase (GPX) is one of the important members of the antioxidant enzyme family. It can catalyze the reduction of hydroperoxides with glutathione to protect cells against oxidative damage. Single-chain variable fragment (scFv) can be converted into seleniumcontaining single-chain variable fragment (Se-scFv) by chemical modification of the hydroxyl groups in scFv, thus Se-scFv possesses GPX activity and becomes a prodrug. To improve the expression of scFv and simplify its purification steps, Single-protein production (SPP) system was used to express scFv and chemical modification was used to synthesize Se-scFv. Therefore, we must construct a new scFv-WCD1-lessACA gene, which can express its mRNA not containing any ACA sequences and express its amino acid sequence of target protein (scFv) being same to scFv-WCD1. In this way, the scFv-WCD1-lessACA can be only expressed in SPP system and no other background proteins in the cells could be expressed. The expression results showed that high level of scFv-WCD1-lessACA synthesis was at least sustained for 96 h in the virtual absence of background protein synthesis. Then, selenocysteine (Sec) was incorporated into the scFv-WCD1-lessACA by chemical modification and resulted in Se-scFv-WCD1-lessACA. The enzymatic characteristics of Se-scFv-WCD1-lessACA were determined. GPX activity was 2,563 U/μmol,its binding constant for GSH was 0.687 ×105/mol. Moreover,Se-scFv-WCD1-lessACA was confirmed to have a strong antioxidant ability to protect mitochondria against oxidative damage induced by Vc/Fe2+ (mitochondrial damage model),suggesting that Se-scFv-WCD1-lessACA has potential application for protection of mitochondrial damage induced by reactive oxygen species (ROS).

A MIXED CORE FOR SUPERCRITICAL WATER-COOLED REACTORS

Cheng, Xu,Liu, Xiao-Jing,Yang, Yan-Hua Korean Nuclear Society 2008 Nuclear Engineering and Technology Vol.40 No.2

In this paper, a new reactor core design is proposed on the basis of a mixed core concept consisting of a thermal zone and a fast zone. The geometric structure of the fuel assembly of the thermal zone is similar to that of a conventional thermal supercritical water-cooled reactor(SCWR) core with two fuel pin rows between the moderator channels. In spite of the counter-current flow mode, the co-current flow mode is used to simplify the design of the reactor core and the fuel assembly. The water temperature at the exit of the thermal zone is much lower than the water temperature at the outlet of the pressure vessel. This lower temperature reduces the maximum cladding temperature of the thermal zone. Furthermore, due to the high velocity of the fast zone, a wider lattice can be used in the fuel assembly and the nonuniformity of the local heat transfer can be minimized. This mixed core, which combines the merits of some existing thermal SCWR cores and fast SCWR cores, is proposed for further detailed analysis.

Stabilized finite element technique and its application for turbulent flow with high Reynolds number

Cheng Huang,Bao Yan,Jinquan Xu,Dai Zhou 한국풍공학회 2011 Wind and Structures, An International Journal (WAS Vol.14 No.5

In this paper, a stabilized large eddy simulation technique is developed to predict turbulent flow with high Reynolds number. Streamline Upwind Petrov-Galerkin (SUPG) stabilized method and three-step technique are both implemented for the finite element formulation of Smagorinsky sub-grid scale (SGS) model. Temporal discretization is performed using three-step technique with viscous term treated implicitly. And the pressure is computed from Poisson equation derived from the incompressible condition. Then two numerical examples of turbulent flow with high Reynolds number are discussed. One is lid driven flow at Re = 10^5 in a triangular cavity, the other is turbulent flow past a square cylinder at Re = 22000. Results show that the present technique can effectively suppress the instabilities of turbulent flow caused by traditional FEM and well predict the unsteady flow even with coarse mesh.